Folic acid and pyridoxine are essential vitamins for man. Both play vital roles in cell replication, maturation and production of intracellular proteins and heme pigments. A number of disease states have been associated with abnormalities in the folic acid and pyridocine metabolism with resulting defects in hematopoiesis and hepatic cell function. The objective of the proposed research is, therefore, to gain better understanding of the biochemical, physiological mechanisms involved in the intracellular metabolism of these vitamins. In the area of folic acid, attention will be given to studies of folic acid transport, including tissues uptake and storage, congener formation, development of polyglutamate stores, tissue store release, biliary excretion and recirculation through the enterohepatic cycle. From preliminary studies it would appear that the enterohepaticfolate cycle is a key factor in folate homeostasis in man and a pathway which is quite sensitive to the adverse affects of disease states and/or toxins. Intracellular pyridoxine metabolism will be studied to characterize the relationship of this vitamin to intracellular enzymes and a potential role in cell metabolism. In the case of both vitamins, points of interruption of the normal metabolic pathways will be searched for to assist in the planning of specific therapeutic interventions.